Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21426 | 64501;64502;64503 | chr2:178586625;178586624;178586623 | chr2:179451352;179451351;179451350 |
| N2AB | 19785 | 59578;59579;59580 | chr2:178586625;178586624;178586623 | chr2:179451352;179451351;179451350 |
| N2A | 18858 | 56797;56798;56799 | chr2:178586625;178586624;178586623 | chr2:179451352;179451351;179451350 |
| N2B | 12361 | 37306;37307;37308 | chr2:178586625;178586624;178586623 | chr2:179451352;179451351;179451350 |
| Novex-1 | 12486 | 37681;37682;37683 | chr2:178586625;178586624;178586623 | chr2:179451352;179451351;179451350 |
| Novex-2 | 12553 | 37882;37883;37884 | chr2:178586625;178586624;178586623 | chr2:179451352;179451351;179451350 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs1235011285  |
-1.136 | 0.901 | N | 0.675 | 0.248 | 0.528561964389 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 0 | 0 |
| L/F | rs1235011285 |
-1.136 | 0.901 | N | 0.675 | 0.248 | 0.528561964389 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.43E-05 | 0 | 0 | 0 | 0 |
| L/F | rs1235011285 |
-1.136 | 0.901 | N | 0.675 | 0.248 | 0.528561964389 | gnomAD-4.0.0 | 5.12877E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 4.70736E-05 | 0 | 2.39515E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.2917 | likely_benign | 0.2547 | benign | -1.454 | Destabilizing | 0.775 | D | 0.641 | neutral | None | None | None | None | N |
| L/C | 0.461 | ambiguous | 0.4593 | ambiguous | -0.815 | Destabilizing | 0.996 | D | 0.679 | prob.neutral | None | None | None | None | N |
| L/D | 0.9373 | likely_pathogenic | 0.9144 | pathogenic | -0.725 | Destabilizing | 0.987 | D | 0.785 | deleterious | None | None | None | None | N |
| L/E | 0.7427 | likely_pathogenic | 0.6745 | pathogenic | -0.54 | Destabilizing | 0.987 | D | 0.773 | deleterious | None | None | None | None | N |
| L/F | 0.2354 | likely_benign | 0.2156 | benign | -0.655 | Destabilizing | 0.901 | D | 0.675 | prob.neutral | N | 0.404137363 | None | None | N |
| L/G | 0.7083 | likely_pathogenic | 0.665 | pathogenic | -1.934 | Destabilizing | 0.961 | D | 0.76 | deleterious | None | None | None | None | N |
| L/H | 0.4492 | ambiguous | 0.4145 | ambiguous | -1.263 | Destabilizing | 0.995 | D | 0.789 | deleterious | N | 0.447986927 | None | None | N |
| L/I | 0.0903 | likely_benign | 0.0851 | benign | -0.127 | Destabilizing | 0.003 | N | 0.244 | neutral | N | 0.411103407 | None | None | N |
| L/K | 0.6001 | likely_pathogenic | 0.5298 | ambiguous | -0.801 | Destabilizing | 0.961 | D | 0.704 | prob.neutral | None | None | None | None | N |
| L/M | 0.1051 | likely_benign | 0.1059 | benign | -0.196 | Destabilizing | 0.923 | D | 0.68 | prob.neutral | None | None | None | None | N |
| L/N | 0.6888 | likely_pathogenic | 0.6331 | pathogenic | -1.037 | Destabilizing | 0.987 | D | 0.791 | deleterious | None | None | None | None | N |
| L/P | 0.9747 | likely_pathogenic | 0.9638 | pathogenic | -0.543 | Destabilizing | 0.983 | D | 0.786 | deleterious | N | 0.47523358 | None | None | N |
| L/Q | 0.3658 | ambiguous | 0.329 | benign | -0.876 | Destabilizing | 0.987 | D | 0.737 | prob.delet. | None | None | None | None | N |
| L/R | 0.4916 | ambiguous | 0.4304 | ambiguous | -0.695 | Destabilizing | 0.983 | D | 0.716 | prob.delet. | N | 0.518540304 | None | None | N |
| L/S | 0.5247 | ambiguous | 0.4772 | ambiguous | -1.803 | Destabilizing | 0.961 | D | 0.703 | prob.neutral | None | None | None | None | N |
| L/T | 0.2881 | likely_benign | 0.2435 | benign | -1.468 | Destabilizing | 0.775 | D | 0.699 | prob.neutral | None | None | None | None | N |
| L/V | 0.083 | likely_benign | 0.0825 | benign | -0.543 | Destabilizing | 0.075 | N | 0.475 | neutral | N | 0.400286194 | None | None | N |
| L/W | 0.6262 | likely_pathogenic | 0.6003 | pathogenic | -0.928 | Destabilizing | 0.996 | D | 0.737 | prob.delet. | None | None | None | None | N |
| L/Y | 0.5546 | ambiguous | 0.5345 | ambiguous | -0.561 | Destabilizing | 0.961 | D | 0.687 | prob.neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.